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    PESTICIDE RESIDUES IN FOOD - 1980


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1980





    Joint meeting of the
    FAO Panel of Experts on Pesticide Residues
    in Food and the Environment
    and the
    WHO Expert Group on Pesticide Residues
    Rome, 6-15 October 1980




    PHENTHOATE

    IDENTITY

    Chemical name (IUPAC): S-alpha-ethoxycarbonylbenzyl
    O,O-dimethyl-phosphorodithioate

    Synonyms:                     Cidial(R), Elsan(R), L 561, ENT
                                  27386, OMS 1075

    Structural Formula:

    CHEMICAL STRUCTURE 1


    Molecular formula:            C12H17O4PS2

    Molecular weight:             320.4

    Colour:                       reddish yellow

    Melting point:                17.5  0.5C

    Boiling point:                the compound decomposes at normal
                                  pressure before reaching the boiling
                                  point.

    Vapour pressure:              4  10-5 torr at 40C

             20
    Density d                     1.226
              4
                                   20
    Refractive index:             d   /1.552 approx.
                                    D

    Flash point (/Cleveland):     165C approx.

    Partition coefficient:        Octanol//water log P = 3.69, 3.82 at
                                  two concentrations

    Solubility of pure compound:  in water at 24C approx 10 mg/l.

    Solubility of technical grade material:  miscible in all proportion
    with acetone, benzene, carbon disulphide, carbon-tetrachloride,
    cyclohexane, cyclohexanone, dioxane, ethanol, ethyl ether,
    methanol, methyl cellosolve; soluble at 2OC 200 mg/l in water, 120
    g/l in n-hexane, 17% in ligroin, above 20% in diethylene glycol and
    above 100 g/l in petroleum solvent.

    Stability of technical material:  after one year of storage at room
    temperature in the original sealed containers, the decrease of the
    active ingredient content is about 1-2% of the original value.  The
    active ingredient content decreases by 1-4% after one month at
    50C.  In water-ethanol 1:1 solutions buffered to pH 3.9, 5.8 and
    7.8 the degradation of phenthoate is relatively slight after about
    20 days.  At pH 9.7 the degradation is approximately 25% after 20
    days. 

    Typical composition of the technical material: 92% ai minimum

    Formulations: Cidial E-4, Cidial 50L, Cidial 50% ES, Cidial AS,
    Cidial ULV, Elsan 50 EC, Elsan dust (2%), Elsan 40WP


    DATA CONSIDERED FOR DERIVATION OF ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

    Phenthoate is rapidly absorbed, distributed, and metabolites
    excreted following oral administration to female mice (3-4 months
    of age). Within 24 hours following administration using either 14C
    or 32P-radiolabelled phenthoate, at dosage levels ranging from 17
    to 161 mg/kg, all administered radioactivity was recovered,
    predominantly in urine (over 90%) and faeces.  The major residues
    found in urine were water-soluble degradation products (Takade et
    al, 1976).

    Biotransformation

    Phenthoate is metabolised rapidly in the mouse with the major
    portion of the molecule degraded and the products appearing in
    urine within 24 hours of administration.  The metabolic sequence
    appears to follow that noted with a variety of other
    organophosphorous compounds and includes both oxidative and
    hydrolytic degradation (Takade et al, 1976).

    The metabolic fate of phenthoate was examined in a cow administered
    a daily dose of 20 mg/kg (relative to its dietary intake) for eight
    days.  Urinary metabolites, isolated over the course of the study,
    were identified as phenthoate acid and desmethyl phenthoate acid. 
    No other metabolic products were identified (Wargo, 1975).

    A proposed metabolic pathway for mammalian species is shown in
    Figure 1.

    FIGURE 1

    Effects on enzymes and other biochemical parameters

    Groups of rats (15 males and females/group) were administered
    phenthoate orally for 90 days at daily dosage levels of 0, 2.5,
    5.0, 12.5 or 25 mg/kg bw.  Plasma, erythrocyte, and brain
    cholinesterase were the most sensitive, being inhibited about 50%
    of normal at the highest dose (plasma was slightly less inhibited). 
    No significant inhibition was observed at 5 mg/kg (Trabucchi,
    1965).  Also see Special Studies on Potentiation for studies on the
    effects of organophosphate esters on serum and liver
    carboxyesterases, enzymes directly involved in the degradation of
    phenthoate.


    TOXICOLOGICAL STUDIES

    Special studies on reproduction

    Rats

    Two almost identical reproduction studies were performed.  In both
    studies, groups of rats (8 male and 16 female rats/group) were fed
    phenthoate in the diet at dosage levels of 0, 10, 30, or 100 mg/kg
    and subjected to a standard 2-litter per generation, 3 generation
    reproduction study.  Animals were fed phenthoate from 21 days of
    age until 100 days of age when they were mated to initiate the
    study.  The first litters were weaned at 21 days, examined, and
    discarded.  The parental animals were again mated to provide a
    second litter, which became the parental animals for the second
    generation.  Eight males and 16 females from the second litters of
    each generation were selected for the succeeding generation.  Gross
    pathology examinations were performed on the second litters of each
    generation.  In one of the studies, gross and microscopic
    examinations of selected tissues and organs were conducted on males
    and females in the control and high-level group of each parental
    generation and on the second litter of the third generation
    animals.  Additionally, in one of the studies, cholinesterase
    activity was measured in male and female animals following weaning
    of the second litter.  This was conducted on both the parental and
    weanling animals with respect to plasma, erythrocyte and brain
    cholinesterase activity.  Although these two latter parameters were
    not evaluated in one reproduction study, gross pathological
    examinations were made.

    Reproduction indices, including mating, fecundity, male and female
    fertility, gestation, and lactation, were calculated and compared
    with control values.  All pups were examined for physical
    abnormalities and viability.

    With the exception of a slightly depressed erythrocyte
    cholinesterase activity observed at 100 mg/kg in all generations of
    both parents and weanlings, there were no significant effects of
    phenthoate on any reproduction parameter measured in the study.  In
    both studies, there were no differences with respect to any of the
    indices observed, and it was considered that phenthoate, at dietary

    dosage levels up to and including 100 mg/kg displays no reproduction 
    hazard to rats (Pfeifer et al, 1975; Wright et al, 1975).

    Special study on teratogenicity

    Groups of rabbits (17 pregnant New Zealand albino rabbits/group)
    were administered phenthoate orally at dosages of 0, 3 or 10 mg/kg
    body weight from days 6 through 18 of gestation in a standard
    teratology bioassay.  A positive control with thalidomide (50 mg/kg
    bw), administered during gestation, was included in the study.  On
    day 29 of gestation, all pregnant animals were sacrificed and
    foetuses delivered by caesarean section.

    There was no mortality attributable to phenthoate.  The data
    related to reproduction (implantation sites, resorption sites, and
    live young) were not affected by phenthoate at the highest dose
    level studies. There were no external or internal abnormalities
    (teratogenic events) associated with phenthoate treatment of
    pregnant rabbits.  Growth of the foetuses was unaffected as was
    survival of young for 24 hours after delivery.  Internal
    development, including somatic and skeletal development, was
    normal.  There were no teratogenic effects noted on the
    administration of phenthoate to pregnant rabbits during the
    critical period of organogenesis.

    In contrast to the lack of teratogenic response with phenthoate,
    thalidomide reduced the number of live young, increased the number
    of resorption sites, and reduced foetal viability.  Several of the
    foetuses exhibited external somatic and skeletal abnormalities
    suggesting that the strain of rabbit used in the study was
    susceptible to eliciting a chemically-induced teratogenic response.

    Treatment of rabbits with phenthoate during gestation (foetal
    organogenesis) did not induce a teratogenic response (Ladd. et
    al, 1975).

    Special studies on mutagenicity

    Mammalian tests

    In two identical studies, groups of male mice (12 mice/group) were
    administered phenthoate as a single intraperitoneal injection at
    dosage levels of 0, 150 or 300 mg/kg bw.  Each animal of each group
    was mated with groups of three untreated, virgin females for a
    period of one week after which the females were removed and
    replaced by another group of females.  This procedure continued for
    six consecutive weeks, the period required for maturation of the
    male germ cell.  Females were sacrificed approximately one week
    after breeding and the number of implantation sites, resorption
    sites, and embryos were recorded.  Data were collected with respect
    to early and late deaths.

    There was no mortality in male mice attributable to the phenthoate
    treatment; the high-dose group was slightly hypoactive for 3-4

    hours after treatment.  Pregnancy rates of females mated to males
    receiving 300 mg/kg was slightly lower than the control values for
    weeks 4 and 6.  The numbers of implantation sites, resorption
    sites, and embryos from females mated with treated males were the
    same as those from control matings.  There were essentially no
    differences between treatment groups and controls with respect to
    mutation rates indicating that, in this in vivo mutagenicity
    study, phenthoate is not a mutagen affecting male germinal cells
    (Arnold et al, 1974; 1975).

    Microbiological tests

    An evaluation of the mutagenicity potential of phenthoate was
    performed using the standard Ames assay and other microbial test
    systems.  Strains of Salmonella typhimurium (TA1535, TA1538,
    TA98 and TA100), with and without a metabolic activation system S-9
    derived from rat liver-induced with Aroclor 1254, were tested at
    concentrations up to and including 2 mg/plate in an effort to
    evaluate genetic mutations.  Standard positive control chemicals
    were used (2-AAF, 2-AA, and B(a)P) in the presence of the metabolic
    activation system and (MMNG, 2NF, and 9-AA) in the absence of the
    metabolic activation system.

    Under the conditions of the experimental assay, phenthoate showed
    no mutagenic activity towards these strains of microorganisms
    either in the presence or in the absence of an enzymatic metabolic
    system. (Carneri, 1979).

    A similar study with Salmonella  typhimurium was reported
    where phenthoate was tested at concentrations up to and including
    5 mg/plate, in the presence and absence of a male rat liver
    metabolic activation system.  In addition, two strains of E.
    coli WP-2 were tested for mutagenicity at the same
    concentrations.  Again, there was no evidence of mutagenicity,
    either in the presence or absence of the metabolic activation
    system utilised, with either species tested (Shirasu, et al,
    1976).

    The recombination-capacity of B. subtilis (H-17 and M-45) was
    tested following exposure to phenthoate.  Phenthoate did not
    prohibit growth in this assay, again demonstrating no mutagenic
    potential (Shirasu et al, 1976).

    A standard, host-mediated assay was performed with mice, utilising
    S. typhimurium as an indicator strain.  Phenthoate was
    administered to groups of 6 mice at dosage levels of O, 100 or 300
    mg/kg body weight by oral intubation for two consecutive days. 
    After the second dosing, the indicator strain was administered to
    the peritoneal cavity, recovered and grown and the mutagenic
    potential of phenthoate evaluated.  The number of reverted colonies
    did not increase as a result of in vivo phenthoate treatment
    suggesting that, under the conditions of this microbial assay,
    phenthoate is not mutagenic (Shirasu et al,  1976).

    Special studies on neurotoxicity

    Chickens

    Groups of adult hens, fasted for 16 hours, were administered
    phenthoate orally at dosage levels of 0 or 2,990 mg/kg bw (a
    previously observed LD50 value).  A positive control (TOCP, 0.5
    mg/kg) was also used.  Ten animals were employed in each test
    group.  With the exception of the TOCP treatment, the single dose
    was repeated following a 21-day observation period.  At the
    conclusion of the study (42 days), all surviving birds were
    sacrificed and subjected to gross and microscopic examinations for
    axon and myelin disruption.  These included the brain, sciatic
    nerve, and spinal cord.

    There were no signs of delayed neurotoxicity observed with
    phenthoate following both treatments although half of the animals
    died over the course of the study.  The positive control animals
    (TOCP) were observed to lose weight and on microscopic examination
    were found to display myelin and axon disruption in the spinal cord
    and sciatic nerve.  Axon degeneration and myelin disruption were
    not seen in the brain of the TOCP-treated animals.  Based on the
    results of this study, it was concluded that phenthoate does not
    induce a delayed neurotoxic reaction similar to that seen with TOCP
    in adult chickens (Fletcher et al, 1976).

    Groups of hens (10 adult hens/group) were administered phenthoate
    orally at dosage levels of 0, 10, 50, 100 or 750 mg/kg/bw to assess
    the delayed-neurotoxic potential of phenthoate.  Animals
    administered the highest dose level were also administered atropine
    and 2-PAM to control cholinergic signs of poisoning.  A positive
    control of TOCP (1,000 mg/kg) and an untreated negative control
    were included in the study.

    When mortality was observed at the highest dose level, a second
    group of hens was introduced using this dose level.  These, too,
    were protected from the acute cholinergic signs of poisoning.  In
    all phenthoate and negative control animals, there were no clinical
    or histological signs of delayed neurotoxicity, although acute
    signs of cholinergic stimulation were evident with phenthoate.  The
    positive control animals, administered TOCP, exhibited ataxia,
    paralysis, and standard signs of delayed neurotoxicity. 
    Histological examination of the TOCP animals revealed a significant
    number of animals with histological defects in the nervous tissue. 
    Based upon this bioassay, phenthoate does not induce a
    delayed-neurotoxic reaction in hens (Good et al, 1979).

    Special studies on potentiation

    Pellegrini and Santi (1972) have reported on the potentiating
    effect of a series of common organophosphorous compounds found as
    impurities in technical phenthoate (as well as other methyl
    organophosphate esters).  Several of the trimethylphosphate


    impurities substantially potentiate the acute toxicity of 
    phenthoate, probably through interaction at the carboxylic acid 
    portion of the molecule. Similar results (with respect to increased 
    acute toxicity when combinations of OP's were tested) were obtained 
    with malathion, providing evidence for the inhibition of 
    carboxyesterase activity as a primary mode of action in this 
    potentiation.

    The acute LD50 of phenthoate was seen to change substantially as
    the presence of impurities in technical mixture increased.  A
    highly purified phenthoate technical sample (98.5%) had an oral
    LD50 in rats of 4,728 mg/kg body weight.  As the content of
    impurities increased, the rat oral LD50 value decreased (90.50% =
    LD50 of 242 mg/kg; 78.7% = 118 mg/kg; 61.2% = 77.7 mg/kg).  Two
    impurities, O,S,S-trimethyl phosphorodithioate and O,O,S-trimethyl
    phosphorothioate, were found to be extremely active in potentiating
    the oral LD50 in rats.  Fukuto and his coworkers (Stevens and
    Fukuto, 1980; Umetsu et al, 1980; Mallipudi et al, 1980;
    Hammond et al, 1980) have recently confirmed this potentiation
    and its probable mode of action.  In in vitro studies,
    hydrolysis of phenthoate by rat liver and serum carboxyesterases
    was examined in the presence and absence of these two impurities.
    Phenthoate acid was the exclusive degradation product obtained with
    the carboxyesterases.  In the presence of impurities, the rate of
    hydrolysis of phenthoate to phenthoate acid was substantially
    diminished, supporting the conclusion that inhibition of
    carboxyesterases is the primary cause of potentiation of phenthoate
    toxicity.

    Special study for carcinogenicity

    Mice

    Groups of mice (50 male and 50 female (Charles River) mice/group)
    were fed phenthoate in the diet at dosage levels of 0, 500 or 1000
    mg/kg for 18 months.  The animals were examined daily for mortality
    and adverse behaviourial reactions.  At the conclusion of the
    study, growth and microscopic examination of tissues and organs was
    performed. Microscopic analysis of 10 animals of each sex surviving
    the 18-month treatment was performed, as were microscopic studies
    on animals that were sacrificed or had died during the course of
    the study.  All neoplasms and tissues with suspected neoplasms were
    examined histologically.  Complete pathological examinations were
    made specifically to identify neoplastic lesions.

    There were no unusual behaviourial changes or increases in
    mortality over the course of the study attributable to the presence
    of phenthoate.  At the conclusion of the study, histological
    examination revealed no treatment-related lesions among any of the
    animals.  The lesions that did occur were considered to be
    naturally occurring, not attributable to the presence of phenthoate
    and not unusual for the strain of mice.  Although a substantial
    number of animals that died were not examined histologically

        TABLE 1.  Acute Toxicity
                                                                                       
    Species        Route       Sex    LD50 mg/kg bw  Reference
                                                                                       

    Rat            Oral2     M+F    245-440            Salvaneschi, 1968; He & Gera,
                                                       1978a; Toyoshima et al, 1978;
                                                       Trabucchi, 1965; Pellegrini &
                                                       Santi, 1972.
                               M      270 (231-316)    Toyoshima et al, 1978.
                               F      255 (216-301)    Toyoshima et al, 1978.
                    IP         M+F    720 (672-77)     Re and Gera, 1975b
                               M      720 (634-868)    Toyoshima et al, 1971.
                               F      745 (615-901)    Toyoshima et al, 1971.
                    SC         M+F    >2000            Toyoshima et al, 1971.
                   Dermal      M+F    2100             Re and Gera, 1978c
                                      (1522-2898)
                               M+F    >5000            Toyoshima et al, 1968.

    Mouse          Oral        M+F    360-840          Salvaneschi, 1968; Re and Gera,
                                                       1978b; Trabucchi, 1965;
                                                       Pellegrini & Santi, 1972.
                    IP         M+F    420-430          Toyoshima et al, 1971.
                    IV         M+F    >250             Salvaneschi, 1968.
                    SC         M+F    >2000            Toyoshima, et al, 1971.

    Dog            Oral               >500             Salvaneschi, 1968.
                                      ca 500           Trabucchi, 1965.

    Guinea pig     Oral               377              Salvaneschi, 1968; Pellegrini
                                                       & Santi, 1977.
                                      ca 400           Trabucchi, 1965.

    Rabbit         Oral               ca 210           Salvaneschi, 1968; Pellegrini
                                                       & Santi, 1972.
                   Dermal             1830             Re and Gera, 1978d.
                   (unabraded skin)   (1194-1595)
                   Abraded skin       2220             Re and Gera, 1978d.
                                      (1872-2697)

    Hare                       M      72               Pellegrini & Santi, 1971.

    Chicken        Oral               ca 2551        Salvaneschi, 1968; Pellegrini
                                                       & Santi 1972.
                                      2990             Fletcher et al, 1976
                                                                                       
    1 This value was obtained with technical product of 90.5% purity.  A purified
    technical product had an LD50 of 2800 mg/kg. (See the section on potentiation
    for an explanation).
    2 The acute oral toxicity of phenthoate oxon is 63 mg/kg bw (Pellegrini and
    Santi, 1972).
    
    because of autolysis, a sufficient number of survivors were
    available to evaluate the carcinogenic potential. In this study, 
    phenthoate was not a carcinogen in mice (Oscarson et al, 1976).

    Toxic signs of poisoning were similar to those noted with other
    cholinergic organophosphate esters.  Mortality occurred within 1-10
    hours following acute intoxication.  Signs of poisoning included
    salivation, lacrimation, slowed or laboured respiration, tachycardia,
    exophthalmus, tremors and convulsions followed by death.

    No antidotal studies were reported, although it is probable that
    atropine and 2-PAM will be therapeutic in the event of acute
    overexposure.

    Phenthoate (technical product) applied to the skin of rabbits was
    found to be non-irritating, inducing a slight erythema 24 hours after
    treatment (Re and Gera, 1978e).  Formulated phenthoate is extremely
    irritating (see short-term dermal studies in rabbits).

    As with dermal studies, technical phenthoate, administered to the
    conjunctival sac of rabbits, was found to be a non-irritant.  However,
    a formulation of phenthoate was irritating, increasing in its
    irritability properties for 2-3 days after administration and
    producing lasting effects for up to 14 days after treatment.  While
    phenthoate is not an irritant as a technical product, the formulated
    products are irritants (Re and Gera, 1975a).

    Acute toxicity studies examining the stability of formulated
    phenthoate during storage have shown an increased toxicity when the
    product was stored at 40C for 12 months.  The acute oral LD50 value
    decreased from 258 mg/kg at the inception of the study to 130 mg/kg at
    one year.  The rate of change of acute toxicity was as shown in Table
    2.

    TABLE 2. Change of acute toxicity with time

                                   
    Storage Time        LD50
     (months)          (mg/kg)
                                   
        0           258 (217-307)
        1           282 (185-430)
        3           200 (163-244)
        6           119
       12           130 (100-170)
                                   

    (Noakes, 1963)


    All samples produced similar signs of poisoning but those stored for 6
    months or longer had a more rapid onset of toxic signs.  The increased
    toxicity may be as a result of formation of the trimethylthiophosphate

    impurities known to potentiate the acute toxicity of phenthoate (see
    Special studies on potentiation).

    Short-term studies

    Rabbit - dermal

    In a series of three short-term dermal studies, a phenthoate
    formulation was administered to rabbits and its dermal toxicity
    evaluated.  Groups of young adult rabbits (5 male and 5 female (3 of
    each sex were tested at the two lowest doses) New Zealand albino
    rabbits/group) were administered phenthoate (Cidial(R) E-4) dermally,
    five days per week for three weeks to intact or abraded skin at dosage
    rates of 2, 20, 75, 200, or 400 mg/kg/bw.  Negative controls were run
    with each test.  Animals were observed daily for mortality and growth
    was evaluated by body weight changes at weekly intervals.  At the
    beginning and at the end of the study, haematologic, clinical
    chemistry, and urine analyses ware performed.  Cholinesterase activity
    was measured only in those rabbits treated at dosage levels below 200
    mg/kg.  Growth and microscopic examinations were performed on a
    variety of tissues and organs in all animals.  Over the course of the
    studies, mortality was reported, primarily in the 400 mg/kg dosage
    group.  Hyperactivity was noted in all treated animals.  It was
    observed that at all dosage levels, the phenthoate formulation was
    severely irritating to the skin and probably contributed to the
    hyperactivity.  Muscular fibrillations were observed in all animals at
    the highest dose level.  Significant body weight loss was observed in
    all treated animals at the highest dose level.  There were no unusual
    effects noted in the haematologic, clinical chemistry, or urinalysis
    parameters.

    Significant erythrocyte cholinesterase was observed at 75 mg/kg in
    both abraded and non-abraded groups.  Plasma cholinesterase was only
    slightly affected, predominantly toward the end of the treatment
    period.  The effect of phenthoate on blood cholinesterase appeared to
    be cumulative, reaching maximal levels towards the end of the
    treatment interval.  After the dosing ended, plasma cholinesterase
    recovered rapidly while erythrocyte cholinesterase, depressed at the
    conclusion of the study, was still approaching normal 21 days after
    the last treatment.  No inhibition of cholinesterase was observed at
    20 mg/kg.

    There were no significant gross or microscopic changes noted, with the
    exception of dermal changes characterised by pale red erythema, slight
    to moderate edema, moderate desquamation and superficial escharosis.
    Microscopic examination also revealed dermal changes in the epidermis,
    predominantly at the high dose level.  There were no other gross or
    microscopic changes attributable to the administration of phenthoate
    (Brett et al, 1974a; 1974b; Paa et al, 1974).

    Groups of rabbits (2 male and 2 female rabbits/group) were
    administered phenthoate dermally, to the intact or abraded skin, 5
    days/week for 3 weeks at dosage levels of 0, 10, 50 or 100 mg/kg bw.

    Growth, physical appearance and behaviour, food consumption, clinical
    chemistry, haematology, and urine analyses were performed.  At the
    conclusion of the study, absolute and relative organ weights were
    obtained on gross examination.  Microscopic examinations of tissues
    and organs were also performed.

    Mortality was observed, as 1 male and 1 female administered 100 mg/kg
    (intact skin) died during the course of the study.  These animals had
    shown severe signs of poisoning and mortality was attributable to the
    phenthoate treatments.

    An apparent anaemia (normocytic) was observed predominantly in the
    survivors of the high-dose group.  It was characterized by reduced
    haematocrit, haemoglobin and red blood cell concentrations.  A
    dose-related reduction of cholinesterase activity was also noted.  Red
    blood cell, plasma and brain, cholinesterase activity were depressed
    at all dose levels.  No other significant effects were noted with
    respect to clinical chemistry, haematology, and urinalyses.  Organ
    weight data as well as gross and microscopic pathology were not
    unusual.  Other than severe dermatitis, there were no pathological
    effects noted in the study (Serota et al, 1979).

    Rat - dietary

    Groups of rats (10 male and 10 female, Donryu rats/group) were fed
    phenthoate in the diet at dosage levels of 0, 5, 10, 30, 100, 300 or
    1000 mg/kg for 3 months.  Animals were observed daily for behaviourial
    changes and growth was recorded at weekly intervals.  At the
    conclusion of the study, haematological, blood chemistry, and urine
    analyses were performed.  Animals were sacrificed at 3 months and
    gross and microscopic examinations of the tissues and organs were
    performed.

    While there were no gross toxic signs of poisoning, growth, especially
    in male rats fed 1000 mg/kg was reduced.  Females receiving 1000 mg/kg
    in the diet displayed a slight depression of body weight during the
    course of the study.  Food consumption data were normal.  At 1000
    mg/kg, there was a significant change in total and differential white
    blood cell counts in both males and females.  Urinalysis data, with
    the exception of slight changes in sodium excretion values in both
    males and females (males increased, females decreased) at 1000 mg/kg,
    did not show changes attributable to the presence of phenthoate in the
    diet.  Slight blood chemistry changes were also observed at 1000 mg/kg
    with respect to several parameters (SGOT, BUN, A/G ratios, and
    cholinesterase activity).  With the exception of cholinesterase
    depression, the other clinical chemistry parameters were not
    substantially different from control values.

    Erythrocyte cholinesterase was significantly depressed in both males
    and females at 30 mg/kg and above.  At 10 mg/kg, a slight reduction of
    activity was reported (less than 25%).  Significant inhibition of
    plasma cholinesterase was noted only in male rats fed 1000 mg/kg.

    There was no significant inhibition of brain cholinesterase at 1000
    mg/kg.

    Gross and microscopic examinations of tissues and organs showed no
    significant effects attributable to the presence of phenthoate at
    dosage levels below 1000 mg/kg.  At 1000 mg/kg several major organs in
    both males and females showed significant weight depression: thymus,
    heart, adrenal glands, testes, and ovaries.  In males, the weight of
    liver, kidney, spleen, and seminal vesicles was decreased while in
    females, the weight of the heart, lung, and uterus was decreased.  The
    gross changes observed at the conclusion of the study were not
    reflected in abnormalities noted on microscopic histopathologic
    examination.

    Based on these studies, a no-effect level is 10 mg/kg (Toyoshima et
    al, 1973).

    Mice

    Groups of mice (10 male and 10 female ICR- mice/group) were
    administered phenthoate in the diet at dosage levels of 0, 5, 10, 30,
    100, 300 or 1000 mg/kg for 3 months.  Growth, as observed by body
    weight changes, was recorded on a weekly basis.  Food and water
    consumption data were recorded and at the conclusion of the study,
    animals were sacrificed for haematological, blood chemistry, and urine
    analyses.  Gross and microscopic examinations of tissues and organs
    were performed at the conclusion of the study.

    There was no mortality observed over the 3-month interval.  Growth was
    depressed at 1000 mg/kg, primarily during the initial parts of the
    study.  After the first month, growth was normal in all test groups.
    Food and water consumption were not affected by the presence of
    phenthoate.  Haematologic values in both males and females showed a
    trend towards a reduction in the total and differential leucocyte
    count in both males and females.  This trend was not significantly
    different from control values at dosage levels below 1000 mg/kg.
    Urinalyses were normal as were all blood chemistry values with the
    exception of cholinesterase activity.  Significant plasma
    cholinesterase depression was observed only at 1000 mg/kg.  At 100
    mg/kg and above, erythrocyte cholinesterase was inhibited.  Brain
    cholinesterase depression was not observed at any dose level.

    On gross examination at the conclusion of the study, organ weight
    changes were observed at 1000 mg/kg.  Male mice showed a significant
    depression of the thymus and adrenal glands, while female mice showed
    significant depression of the weight of heart, lungs, thymus, liver,
    kidneys, spleen, uterus, and ovaries.  On histological examination,
    the tissues of treated animals did not display pathological changes
    attributable to the presence of phenthoate, suggesting that the gross
    changes were physiological adaptation to the high dosage of
    phenthoate.  A no-effect level in the study, based upon cholinesterase
    depression in both males and females, is 30 mg/kg in the diet
    (Toyoshima et al,  1973).

    Dogs

    Groups of dogs (4 female and 4 male, beagle dogs/group) were fed
    phenthoate in the diet at dosage levels of 0, 10, 30, or 100 mg/kg for
    2 years.  Daily examinations were made for clinical signs of poisoning
    or adverse behaviour.  Growth, as evidenced by body weight, was
    recorded weekly as were food consumption data.  At periodic intervals
    (1, 3, 6, 9, 12, 18, and 24 months), haematology, blood chemistry
    (including cholinesterase) and urine analyses were performed.  Plasma
    and erythrocyte cholinesterase determinations were performed at 2, 4,
    6, 9, 13, 26, 78, and 104 weeks and brain cholinesterase analyses were
    conducted at the conclusion of the study.  At the conclusion of 104
    weeks of dietary administration, each dog was sacrificed and gross and
    microscopic examinations of tissues and organs were performed.

    There was no mortality over the course of the study at any dosage
    level.  Growth and food consumption were normal.  With the exception
    of cholinesterase depression, data from blood clinical chemistry
    tests, haematological tests, and urinalyses were normal.  Erythrocyte
    cholinesterase inhibition was observed at 30 mg/kg and above.  This
    effect was first noted 2 weeks after the initiation of the study and
    was relatively constant over the entire study.  Plasma and brain
    cholinesterase activity were unaffected and considered normal at all
    dietary levels.  Gross and microscopic examinations of tissues and
    organs at the conclusion of the study did not show any significant
    effect of the inclusion of phenthoate in the diet at dose levels up to
    and including 100 mg/kg.  A no-effect level in this study, based on
    cholinesterase depression, was 10 mg/kg in the diet equivalent to 0.29
    mg/kg bw, a value derived from the average food consumption values
    over the 2-year period (Nelson et al,  1972).

    Long-term study

    Mice

    (See special study on carcinogenicity).

    Rats

    No data available.


    RESIDUES IN FOOD

    USE PATTERN

    Phenthoate is a wide spectrum insecticide for agricultural and
    domestic use.  It is active against both chewing and sucking insects,
    in particular against lepidopterous larvae, soft scales and larvae and
    adults of some species of mosquitoes.  The pesticide should be applied
    in enough water to insure complete coverage of the foliage, branches
    and fruit when applied as a ground application.

    The registered use patterns reported from Italy, Israel, Japan and
    South Africa are summarised in Table 3.


    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Citrus fruit

    The trials were performed in Brazil, Florida, Italy and South Africa
    with both the recommended and approximately double dose rates.  The
    results are summarised in Tables 5 and 6.  Treatments carried out with
    low volume spraying (about 940 l/ha) or with 0.5% oil additive
    resulted in somewhat higher residue than the dilute application, when
    the spray was applied until run off to achieve full coverage.

    The repeated treatments carried out following the recommended use
    pattern did not increase the residue in the fruit significantly.  The
    colometric method used in 1963-65 experiments showed 3-4 times higher
    residues than those obtained with GLC determination of samples
    deriving from similarly treated plots at later trials.

    The phenthoate residues remain entirely in the peel of fruits.  The
    pulp did not contain detectable residues (limit of determination
    0.02-0-03 mg/kg) at any time after treatment with the exception of two
    sets of experiments.  In one case about 10-25% of the residue found in
    the peel was detected in the pulp at the day of treatment and after 98
    days, respectively.  However in the other experiment the residue in
    the pulp was only about 2.55% of the residue found in the peel and
    decreased with time.

    The phenthoate oxon was only detected in the peel.  Limit of
    determination in the pulp was 0.01 mg/kg (Moye).  The oxon derivative
    amounted to a maximum of 0.12 mg/kg (43%) on lemon, 0.08 mg/kg (15%)
    on grapefruit and 0.62 mg/kg (38%) on orange.  The values in
    parentheses refer to the ratio of oxon to the parent compound.  The
    results of other trials (Iwata, 1979) indicate similar residue ranges.

    The residue, on a whole fruit basis, can be calculated from the
    residue measured in the peel taking into account the peel/pulp weight
    ratio which is fairly constant for different varieties (Iwata, 1977).
    For instance, in the case of valencia orange 1/5 of the peel residue
    can be considered as the residue on whole fruit basis, while for the
    variety Hamlin, the ratio is 1/4.

    Other Crops

    A limited number of supervised trials were carried out on apple, pear,
    cabbage, lettuce, olives, onions, radish, spinach, sweet potato and
    sugarbeet in Italy and Japan in 1962-65.  The results of these
    experiments were provided to the Joint Meeting for evaluation (Tables
    7 and 8).  However they were not considered to represent the current
    use of phenthoate or to be sufficient for evaluation, thus no



        TABLE 3.  Registered Uses of Phenthoate

                                                                                                                     
    Crop             Pest                    ai [g/100R]   Formulation     No. of treatments   Amount of water l/ha
                                                                                                                     

    Citrus           Scale insects       )   50 - 100           EC              1 - 2              1000-10000
                     Aphids              )                    40 WP          (generally)
                     Orange leaf miner   )
                     Leaf rollers        )

    Apple            Codling moth            40 - 50            EC              5 - 10             1000-2500
                                                                WP              1 - 6              5000

    Brassica         Large white butterfly   50 - 1000          EC              1 or more          up to 1000

    Japanese pears   Leaf rollers            40 - 50            WP              1 - 6              3000
                     Fruit moths
                     Mealy bugs

    Nuts             Codling moth               70              EC              3 - 4              2000-10000

    Olives           Black scale              60 - 75           EC              3 - 4              2000-10000
                     Olive thrips

    Onions           Thrips                     75              EC            1 or more            up to 1000

    Pears            Codling moth             40 - 50           EC              3 - 7              1000-2000
                     Pear psylla              200 250                                              200 - 500

    Potatoes         Potato tuber moth          100             EC            1 or more            up to 1000

    Rice (paddy)     Rice stem borers  )      50 - 100          EC              1 - 4              800 - 1500
                     Leaf and plant    )
                     hoppers           )     1.65 - 3.3 kg      EC                1               30-40 aerial
                     Rice bugs         )     0.6-0.8/kg/ha.     Dust
                     Rice leaf beetle  )
                     Rice leaf miner   )
                                                                                                                     
    
    recommendation was made by the Meeting for the maximum residue levels
    in/on these commodities.


    FATE OF RESIDUES

    In animals

    Lactating dairy cattle were administered 14C-labelled phenthoate at
    levels of 1, 5 and 20 mg/kg on feed basis (Wargo, Anonym. 1979).
    Samples of urine, faeces and milk were collected every day during the
    administration for 8, 18, 26 days and withdrawal (7 days).

    The animals were slaughtered the following day and the tissue samples
    were taken.  The total 14C residue measured in various tissues and
    calculated as parent compound at a dose rate of 20 mg/kg is given in
    Table 9.  Muscle and fat did not contain detectable residues at rates
    of 1 and 5 mg/kg.  The residue in the other tissues also decreased at
    the lower rates.

    Total 14C extractable residues in liver and kidney were 29% and 51%
    respectively, and consisted of organosoluble and watersoluble
    metabolites.

    The metabolites were separated with various chromatographic methods. 
    In the liver at least eleven compounds were found, of which the major
    component represented 8% of the total 14C residues in liver.  One of
    the remaining ten was present at a higher concentration than 3%.  The
    unextractable residue was quantitatively released by acidic
    hydrolysis.  At each feeding level the cows with a seven-day
    withdrawal period demonstrated a significant decrease in residues
    compared to the cows sacrificed 24 hours after the last 14C
    phenthoate dose.  Even the "bound" metabolites were eliminated from
    the tissues of kidney and liver.

    The 14C residues in milk reached the plateau on the second or third
    day of treatment.  During the feeding period the total residue
    plateaued at the levels given below:

    Level in diet   Residue in milk, mg/kg

       1 mg/kg           0.001-0.003
       5 mg/kg           0.008-0.026
      20 mg/kg           0.015-0.04

    The residue declined after withdrawal of the pesticide from the diet
    and approached the limit of determination after 3-6 days.

    The 0.04 mg/kg total 14C residue in milk consisted of 7% (0.0028
    mg/kg) organosoluble, 16% (O.006 mg/kg) water-soluble compounds and
    52% (0.019 mg/kg) milk solids.

    The residue level in each fraction was too low for further
    investigation.

    Neither phenthoate nor its oxon could be detected by conventional
    analytical methods based on GLC determination in any of the tissue or
    milk samples (limit of determination 0.01 mg/kg for fat and 0.05 mg/kg
    for the other samples).

    White leghorn laying hens were given feed containing 14C phenthoate
    at 1.8, 5.9 or 26 mg/kg for 30 days.  The birds were sacrificed on
    days 1, 3, 7, 14, 21 and 30 during the treatment and on days 7 and 15
    during the withdrawal period (Huhtanen, 1979a).  The maximum residue
    contents of tissues analyzed are given in table 4.

    TABLE 4.  Residues of phenthoate in tissues of chickens fed phenthoate
    in the diet at various levels for 30 days

                                                                 
    Tissue                  Concentration of phenthoate in diet
                             1.8 mg/kg   5.9 mg/kg   26 mg/kg
                                                                 

    breast muscle              0.333       0.072       0.073
    leg muscle                 0.018       0.035       0.13
    liver                      0.024       0.04        0.48
    kidney                     0.094       0.53        1.3
    skin                       0.039       0.16        0.38
    fat                        0.019       0.07        0.16
    eggs                       0.014       0.058       0.35

    limits of detection

    for non-fatty tissues      0.0077      0.027       0.066
    for fatty tissues          0.016       0.053       0.13
                                                                 


    A plateau of the residue was reached in liver and kidney between the
    third and seventh day of treatment.  In the muscles detectable
    residues were found from 21st day of treatment but no residue was
    detected during the withdrawal period either in the muscles or in the
    eggs.  Less than 10% of the extracted material, which accounted for 70
    of total radioactivity, was of non-polar character in the kidney.  A
    large percentage (50%) of the more polar compounds were acidic.

    No abnormalities were observed in the organs of the hens and the
    production of eggs was not reduced during the treatment period.

    Fish residue studies were carried out with channel catfish and
    bluegill sunfish in order to determine the biomagnification behaviour
    of phenthoate.

    In water containing 14C-phenthoate at 10-6 mg/l level the average
    concentration ratios from catfish tissue/mud and catfish tissue/water
    were 0.17 (0.09-0.33) and 5.76 (2.47-9.97) respectively after 33 days.
    Residue levels in contaminated fishes showed a gradual reduction if
    the fishes were placed in uncontaminated water (Marshall, 1979).

    The uptake and bioaccumulation of 14C-phenthoate residues from soil
    aged for 21 days in the aquaria into channel catfish were studied at
    fortified soil levels of 0.01 and 1 mg/kg.  The residues in the
    catfish "meat" were 0.003 mg/kg 28 days after placing them into the
    contaminated water (Booth, 1978).

    Bluegill sunfish were exposed to 14C-phenthoate at 2.1  10-5 mg/l or
    at 2  10-4 mg/1 in the water of a simulated dynamic water system for
    30 days.  The average bioaccumulation ratio of 14C was 816 and 901
    respectively, while for the edible tissue 240 and 248 were the
    calculated values.  The residues found in tissues of 14-day withdrawal
    samples taken from the higher level tank was only 3% of the level
    found after 30 days of exposure (Huhtanen, 1979b).

    In plants

    Selected leaves and fruit of a Valencia orange tree were treated by
    brush application with a solution of 30 mg phenthoate [32P or 14C] in
    50 cm of water containing 0.06% emulsifier (Takade, 1977).  Samples of
    leaves and fruits were taken 3, 7, 10 and 14 days after treatment and
    rinsed 5 times with acetone to remove the surface material.  After
    rinsing with acetone, the fruit was carefully peeled.  The leaves,
    peel and pulp were cut into small pieces and placed in a vacuum oven
    at 40C for approximately 10 hours.  No loss in radioactivity was
    detected for the drying process.  The dried samples were extracted
    with acetone.  The metabolites were separated on thin layer plates
    using four solvent systems.  The total radioactivity of solid
    materials was then determined by combustion analysis.

    The major portion of phenthoate applied to leaves was lost by
    volatilisation.  The concentration and distribution of residue in
    orange fruit are given in Table 10.  Significant loss in total
    recovery wan observed in fruit.  Less than 1% of the total activity
    applied was detected in the orange pulp.  The majority of the residue
    both in fruit and in leaves was intact phenthoate.  The ratio of
    phenthoate and its phenthoate oxon is shown in Table 11.  Other
    metabolites, desmethyl phenthoate, mandelic acid, bis-alpha-ethoxy
    carbonylbenzyl disulphide, O,O-dimethyl phosphorodithioic acid, O,O-
    dimethyl-phosphorothioic acid and two unidentified compounds amounted
    to 0-5.2% individually.  Glucosidase, hydrochloric acid and sodium
    hydroxide together dissolved about 92-98% of the bound residues in the
    peel.  The major conjugated metabolites were, in order of importance,
    ethyl mandelate, mandelic acid, desmethyl phenthoate and phenthoate
    acid (Mallipudi and Fukuto, 1980).

    Apple, pear and olive trees were treated with 32P-labelled phenthoate
    according to the recommended use pattern (Santi, 1967).  The surface
    of the fruits was washed with methanol to remove the original active
    substance or any other derivatives containing methanol-soluble 32P
    still present on the peel (methanol extract).

    After washing, the various fruits were homogenised in a blender with
    chloroform (chloroform extract).

    The plant filter cake was further extracted with water to separate
    eventual water-soluble compounds (water extract).  The 32P content of
    various extracts and of residual plant was determined radiometrically.
    The phenthoate equivalents of the radioactive residues found at
    certain times after treatments are listed in Table 12.

    Column chromatography, thin-layer chromatography and paper
    chromatography were used for the separation and identification of the
    compounds in the various extracts.

    The probable metabolic pathways are shown in Fig. 2.

    The repeated treatments of apple trees with a solution containing
    0.02% ai (half the dosage usually applied) resulted in qualitatively
    similar picture regardless the number of treatments.  The phenthoate,
    although not systemic, penetrates slightly into the fruits and
    undergoes oxidation and hydrolysis; 15-29 days after treatment 95% of
    water-soluble residue was phosphoric acid while monomethyl and
    dimethyl phosphoric acids were detected in traces.  Phenthoate oxon
    was detected in traces only 1 day after treatment.

    FIGURE 2

    The metabolism of phenthoate in the two varieties of pears showed a
    slightly different pattern.  Phenthoate acid,
    O,O-dimethyl-thio-phosphoric acid, O,O-dimethyl dithio phosphoric
    acid, dimethyl phosphoric acid and phosphoric acid were identified and
    four other unidentified compounds were found in the "water-soluble"
    extract.  The quantity of any of them did not reach 0.1 mg/kg
    phenthoate equivalent.  Intact phenthoate in varying amounts, traces
    of P=O derivative and unidentified compounds were found on the surface
    of olive at different intervals after treatment.  Phenthoate
    penetrated into drupes with subsequent hydrolysis and oxidation
    process and formation of the same metabolites as found in other
    fruits.  The processed oil contained only intact phenthoate (0.14
    mg/kg), while in olive husks 0.23 mg/kg phenthoate and 3 mg/kg of
    other 32P containing compounds were detected.

    A 0.05% emulsified solution of 14C-labelled phenthoate was sprayed on
    cabbage seedlings and brushed over Hime apple fruits and also
    strawberries.  Phenthoate remained mostly on the surface and only
    3.3-6.7% of the total amount penetrated into the plants.  The residue
    decreased rapidly both on the surface and in the plants.  Eight days
    after treatment the residue on the surface of cabbage consisted of 86%
    intact phenthoate, 8% bis-alpha-carbethoxy-benzyl disulphide, 1.9%
    ethyl mandelate and 1.3% unidentified compound.  Phenthoate oxon was
    detectable in traces (0.4-0.7%) during the first day after treatment.
    Within the cabbage seedlings 8 days after treatment intact phenthoate
    was present in an amount of 10.2% and the metabolites identified were
    mandelic acid (46.9%), bis-alpha-carbethoxy-benzyl disulphide (6.5%),
    phenthoate acid (4.8%), desmethyl phenthoate (3.2%), phenthoate oxon
    (1.8%).  Six unidentified compounds were separated (total amount
    18.8%) of which two accounted for 14.3%.  The degradation of
    phenthoate in/on apple took place more slowly than in/on cabbage, or
    strawberry, while the metabolite patterns were rather similar in case
    of apple and strawberry to that found in/on cabbage seedlings (Hirose
    et al, 1971).

    In soil

    The degradation of ring-labelled 14C-phenthoate in a moist (50% of
    capacity) loam and silty clay loam soil was studied (Iwata, 1977b).
    Phenthoate was rapidly degraded by heat-labile soil enzymes which
    converted it to phenthoate acid under both aerobic and anaerobic
    conditions, even with a soil treatment of 100 mg/kg.  Under aerobic
    conditions and in low concentration the phenthoate acid underwent
    extensive microbiological degradation to CO2 (up to 50% of the
    theoretical value) and polar products.  At 100 mg/kg level or under
    anaerobic conditions it degraded by first order kinetics, presumably
    by simple hydrolysis.

    In a loam soil phenthoate at 1.25 and 2.5 mg/kg had no effects on the
    rates of degradation of 14C-cellulose or 14C-starch by soil microbes
    over a 25-day period as measured by the evolution of 14C.  The rate
    of nitrification in soil amended with (NH4)2SO4 was likewise
    unaffected over a 28 days period (Sikka, 1979).

    Phenthoate appears to be relatively persistent under dry soil
    conditions (Iwata, 1977a) and in dry dust adhering to plant surfaces
    (Iwata, 1975).  In two sets of experiments 95% and 62% of the initial
    doses remained unchanged after 59 and 75 days respectively.

    The results indicate that conditions favouring microbial activity,
    such as adequate moisture and warm temperatures, make soil type of
    secondary importance for phenthoate degradation.

    The fate of residues was also studied under field condition (Moye et
    al, undated).  Soil samples were taken from the drip-line and middle
    at 0-6 and 6-12 cm depths under the orange trees treated with Cidial 4
    E solution of 0.03% ai 1, 3, 7, 14 and 28 days after treatment.  Four
    samples were taken from both depths for each time.  The maximum of
    phenthoate concentration was observed at the drip-line on the third
    day (1 mg/kg, in 0-6 cm and 0.68 mg/kg in 6-12 cm).

    The mean residue at 0-6 cm was 0.56 mg/kg which decreased to 0.12
    mg/kg 28 days after treatment.

    Phenthoate oxon was not detectable in any of the experiments.  The
    mobility of phenthoate and its soil metabolites were studied by
    leaching experiments using sandy soil (organic matter 1.6%), silt loam
    (o.m. 6%), sandy loam (o.m. 3.3%), clay loam (o.m. 5.9%) (Anonymous,
    1978a).  The columns were filled to 25.4 cm with the untreated soils
    after prewetting the column with water.  The fortified soil (5 cm) was
    layered over the untreated soil.  For studying the mobility of
    metabolites the fortified soils were aged for 30 days under greenhouse
    conditions.  Water equivalent to 500 mm rain for parent compound and
    to 380 mm for metabolise was allowed to pass through the column and
    analyzed.  The columns were sectioned into four equal lengths for
    analyses by the measurement of radioactivity.  The upper 15 cm of the
    sandy soil contained 72.3% of phenthoate and 85.7% of the metabolites
    while the other soils retained 87.3-88.8% and 89.4-90.9% respectively.
    The water effluent from the light sandy soil contained 8.32% and 6.62%
    of the original activity.  From the other soils the 14C activity in
    the water effluent amounted to 2.9-6.44% and 3.39-4.21%.

    In water

    14C phenthoate was added to 0.01 M sodium phosphate buffers (pH 6.0,
    7.0 or 8.0) to give a final concentration of 1.5  10 -5 M.  Aliquots
    were taken 3, 7, 10, 14, 21 and 28 days after addition of the 14C
    material to the buffer and analyzed an TLC plates subsequent to
    appropriate preparation.

    32P-phenthoate was added to the buffer solutions in a 1  10-4 M
    final concentration and was treated similarly to the 14C compound.

    All solutions were held at 24.5  1C in a constant temperature room.

    The pH of buffered solutions, containing radiolabelled phenthoate
    under similar conditions, was monitored over the experimental period
    and no pH change was detectable.

    Evidently, phenthoate is fairly stable in water at the indicated pH
    values.  45%, 21%, 22% of its initial amount were present after 28
    days at pH 6, 7, 8 respectively.  Its half life is about 12 days at pH
    8.0.  Phenthoate acid was observed in greatest amount (30-55%)
    irrespective of pH.  Hydrolysis of carbonyletoxy moiety appeared to be
    fastest at pH 8.0.  On the other hand the rate of formation of
    desmethyl phenthoate, the second most prominent hydrolysis product,
    was fastest at pH 6.  Phenthoate oxon was not detected at any time.
    Other products indicated in Figure 2 were observed in small amounts
    (Takade, 1977).

    Photodegradation

    The photodegradation of 14C-phenthoate was studied in distilled water
    (pH = 7.00.5) at concentrations of 8 mg/kg and 5 mg/kg (Anonymous,
    1978).

    A medium pressure mercury lamp, fitted with a Pyrex 7740 filter that
    excludes light of wavelength less than 280 nm, was immersed in the
    solution to be irradiated.  After 5 and 8 hours of irradiation,
    aliquots of the photolysed solutions were taken and analyzed applying
    HPLC and TLC techniques.  Approximately 50% of phenthoate had degraded
    after 6-8 hours of irradiation, while there was no loss in another
    phenthoate solution kept in the dark for the same time.  Ethyl
    mandelate was found to be the major degradation product.  In addition
    three unknown products were detected but each of them accounted for
    less than 10% of the parent compound.

    An acetone solution of radiolabelled phenthoate (32P or 14C) was
    applied to glass plates, which were exposed to sunlight daily for 7
    hours (Takade, 1977).

    Air temperature during the exposure ranged from 7.2 to 23.3C.  Under
    these conditions approximately 90% of the applied phenthoate was lost
    after 40 hrs of exposure by volatilisation.

    The unchanged phenthoate gradually decreased in proportion to the
    other alteration product during the exposure (see Figure 2).
    Phenthoate oxon was identified as the major product.  Other products
    isolated were desmethyl phenthoate, mandelic acid, bis-[alpha-carboxy)
    benzyl]-disulphide, bis[alpha-/carbethoxy/benzyl]disulphide and
    O,O-dimethyl phosphorothioic acid.  Results of other experiments
    indicated that elevated temperatures may speed up the phenthoate oxon
    formation and its disappearance.  The latter is also facilitated by
    rainfall (Nigg and Stamper, 1980).

    The degradation products formed upon exposure to sunlight and air on
    glass plates or found on citrus leaves and fruits are essentially the
    same.

    In processing

    The effect of processing was studied on orange, lemon and grapefruit
    treated in the field twice with Cidial 4 E in solutions of 0.03% or
    0.06% ai.  The samples were taken 50, 19 and 18 days after last
    treatment respectively and were processed with a FMC processor.  The
    residue ranges found in 4 samples taken at each stage are summarised
    in Table 13 (Moye et al, undated).

    Little, if any, residue decrease occurred from washing of oranges and
    lemons, which is in good agreement with the findings of Iwata et al,
    who carried out laboratory washing to simulate packing house
    treatment.  On the other hand laboratory washing of the grapefruit
    removed about 50% of the residue found 3 days after treatment and from
    about 25% to less than 10% thereafter.

    Phenthoate seems to be concentrated in the waxes and oils of the rind.
    Fruit juice contained negligible residues (<0.01 mg/kg).  Residues
    found in the dried rind, which is used as a cattle feed, show an
    approximate 44-58% loss of residue during processing and drying.

    The majority of the residue found in/on olives remained in the olive
    husk and the processed oil contained only intact phenthoate (4.1% of
    total residue) (Santi, 1976).


    METHODS OF RESIDUE ANALYSIS

    Methods that have been developed for the determination of phenthoate
    in crops and animal tissues have been reviewed.  Bazzi (undated)
    described a method which is based on acetone extraction, liquid-liquid
    partition clean up on a Plorex column and gas chromatographic
    determination using 3.8% UCCW 982 on Gas Chrom Q packing and a flame
    photometric detector.  The limit of determination is 0.04 mg/kg or
    less depending on the type of sample.  The method is suitable for the
    determination of phenthoate and its oxon in citrus and their processed
    by-products in maize, cattle meat and soil.

    Moye et al (undated) found acetone: acetonitrile 1:1 mixture most
    efficient for the extraction of phenthoate from soil, fruits and
    by-products of citrus processing.  OV-101, OV-17 (Iwata et al, 1979)
    and OV-225 (Moye et al, undated) liquid phases were used to separate
    phenthoate, phenthoate oxon from other organophosphate pesticides also
    applied in citrus orchards.

    Another method for the determination of residues in animal products
    includes extraction by acetonitrile from muscle, kidney and liver, by
    acetone and benzene from milk and by heptane from fat; partition with
    benzene, hexane and acetonitrile; column chromatography on Floricil;
    and GLC determination using 3% OV-101 packing with FPD.  Limit of
    determination: 0.01 mg/kg for milk, 0.05 mg/kg for tissues.  The
    recovery at 0.05-0.1 mg/kg level is about 92% for all samples.

    The basic method described by Bazzi (undated) in combination with the
    other liquid phases and slight modifications proposed by the other
    authors is suitable for regulatory purposes.

    NATIONAL MRL'S REPORTED TO THE MEETING

    Phenthoate is registered in 36 countries all around the world.  Some
    of the maximum residue limits and pre-harvest intervals were reported
    to the meeting.

                                                                     
                                             Pre-harvest
                                              intervals       MRL
                                               (days)       (mg/kg)
                                                                     

    Hungary        apple, pear,
                   sugar-beet                     21          0.5

    Italy          apple, pear, walnut,
                   vegetables, rice               20          0.3
                   citrus, olive                  60          0.3

    Israel         oranges, grapefruit          20-30

    Japan          pear, peach                     7          0.1
                   pumpkin                         1          0.1
                   mandarine, orange              14          0.1
                   rice (unpolished)               7          0.05
                   japanese pear                  30          0.1

    Netherlands    citrus fruit                               0.5

    New Zealand    brassica crops                             0.7

    South Africa   citrus                          21         1.0
                   brassica                         3         1.0
                   onion,potato                     7         0.1

    Sweden         citrus                                     1.0

    USA            citrus                                     2.0
                                                                     



        TABLE 5.  Residues of Phenthoate in oranges

                                                                                                                                               
                                                                                     Residues in mg/kg, at intervals/days/
    Variety              Application                                                           after application                      Reference
    (and part    Country      Year    No.    kg ai/ha      formulation
    of fruit)                                or %                          0-3     7-10    14-19    24-25    31-32    39-45    56
                                                                                                                                               

    Valencia     USA          1973     1      8.5             50 L         0.8     0.5      0.4      0.3      0.2      0.1     0.1    Iwata, 1977a
                 (Florida)             1      4.3             50 L         0.5     0.3      0.2      0.1      0.09     0.09    0.07

    Valencia     USA          1979     1      4.2             4 EC         2.9     2.3      1.5                        0.58    0.23   Iwata, 1979
    (peel)       (Florida)             1      8.4             4 EC         4.0     3.0      2.1                        0.85    0.35
                                       1      8.41            4 EC         6.3     4.2      3.0                        1.4     0.38

    Valencia     USA
    (peel)       (Florida)    1979     2      0.03%3          4 EC         1.65    0.67     0.29                       0.38           Moye et al
    (pulp)                                    0.06%                        0.03    0.04     0.01                       0.01           (undated)

    Hamlin       Brazil       1979     1      0.1%            50 L         1.38    0.79     0.5      0.33              0.22  0.22-0.12 Camargo,1980
    (peel)

    Valencia     Italy        1965     1      0.06%1,2        50 L         4.9     1.6      1        1.1       0.8     0.6            Anonym, 1965

    Moro (peel)  Italy        1963     1      0.05%1,2        50 L         3.2                       1.8                       1.2

    Valencia     Israel       1973     1      7.5+0.5% oil    50 L         1.66    1.08              0.5               0.2            Greenberg
                                       1      10              50 L         0.71    0.58              0.04              0.09    0.02   et al, 1974
                                       1      20              50 L         2.1     1.33              0.75              0.37    0.12
    Shamouti     Israel       1973     1      7.5             50 L         1.02    0.98                                0.45    0.21
                                       1      7.5+0.5% oil    50 L         0.98    1.08                                0.4     0.36
                                       1      15              50 L         1.68    1.41                                0.82    0.4

    Orange       Japan                 3      0.05%           50 EC                0.01     0.008    0.004                            Anonym, 1980
    (pulp)                             5      0.05%                                0.01     0.009    0.009
                                       3      0.05%                                0.02     0.005    0.008
                                       5      0.05%                                0.015    0.006    0.005

    TABLE 5.  Continued...

                                                                                                                                               
                                                                                     Residues in mg/kg, at intervals/days/
    Variety              Application                                                           after application                      Reference
    (and part    Country      Year    No.    kg ai/ha      formulation
    of fruit)                                or %                          0-3     7-10    14-19    24-25    31-32    39-45    56
                                                                                                                                               

    Valencia     S. Africa    1970     1      0.213%          50 L         3.7              2.05                1.1
                              1971     1      0.1%            50 L         1.21             0.56                       0.32    0.23   Anonym, 
                                                                                                                                      1970

    Valencia     S. Africa                                                 0.37             0.3                        0.12
    (pulp)
                                                                                                                                               

    1 Low volume application with a spraying volume of 940 l/ha
    2 Colorimetric method was used for the determination
    3 Three months elapsed between applications; the maximum residue values found in four replicates are given


    TABLE 6.  Residues of Phenthoate in Grapefruit and Lemon

                                                                                                                                               
                                                                               Residues in mg/kg, at intervals/days/
    Variety                                      Application                             after application                       Reference
    (and part    Country      Year    No.    kg ai/ha      formulation
    of fruit)                                or %                          0-4     8-11    18-21    33-35    38-46    60
                                                                                                                                               

    Grapefruit   USA          1978     1      3.4             4 EC                 0.94    0.77              0.48              Iwata, 1979
    (peel)                             1      6.7             4 EC                 2.1     1.6               0.87
                                       1      6.71            4 EC                 3.9     2.5               1.4
                              1979     1      0.03%2          4 EC                 0.9     0.5      0.31
                                              0.06%2                               1.8     0.77     0.59
    (pulp)       USA          1979     2    0.03+0.063,4      4 EC        0.007   0.008   0.011             0.002    <0.002    Moye et al, undated

    Whole fruit  Israel       1973     1      0.075%          50 L         0.97    0.47                      0.23     1.131    Greenberg et al,
                                       1      0-0.75%4        50 L         1.4     0.63                      0.39     0.14     1974
                                       1   0.075%+0.5% oil    50 L         0.84    0.79                      0.93     0.1
                                       2   0.075%+0.5% oil4   50 L         1.0     1.0                       0.74     0.16
                                       1       0.15%          50 L         1.25    1.5                       0.41     2.7
                                       1       0.75%4                      2.0     2.0                       0.57     0.42

    Lemon        USA          1974     1         7            50 L         1.2     0.8      0.6      0.4      0.3      0.3     Iwata, 1979a
    (peel)                    1974     1      1.8             50 L         0.5     0.3      0.2      0.2      0.1      0.1
                              1978     1      4.2             4 EC                 1.5      0.9               0.47
                                       1      8.2             4 EC                 2.8      1.7               0.78
                                       1      8.21            4 EC                 3.8      3.3               2.2
                              1979     1      5               4 EC                 3.7      2.7               1.1
                                              10              4 EC                 7        4.5               1.9              Iwata, 1979
                                              10              4 EC                 14       11                5.7

    Whole fruit  S.Africa     1973     1      0.04%           50 L         0.4     0.26     0.08              0.09             Anonym, 1970
                                              0.1%            50 L         1.4     0.96     0.47              0.17
                                                                                                                                               

    1 Low volume application with a spraying volume of 940 l/ha
    2 Sprays were applied to achieve full coverage
    3 17 days elapsed between applications
    4 The maximum residue values found in four replicates are given.

    TABLE 7.  Residues of Phenthoate in Apple and Pear

                                                                                                                                             
                                                                              Residues in mg/kg, at intervals/days/
    Variety              Application                                                    after application                        Reference
    (and part   Country  Year    No.    kg ai/ha    formulation
    of fruit)                            or %                        0      1      4-7    9      14-17   21-26   29-34   39-46
                                                                                                                                             

    Apple       Italy    19621   1       0.04%          50 L        2.8    1.19    0.47   0.22   0.16    0.11     <0.1           Anonym, 1972
                         1962    1       0.03%          50 L        1.57   0.78    0.34          0.18    0.13             0.1
                         19621   1       0.04%          50 L        1.6    0.93    0.36          0.1              <0.1
                         1962    4       0.04%          50 L        1.92   1.21    0.48          0.12             <0.1

    Pear        Italy    19631   1       0.04%          50 L        1.45   1.1     0.6                   0.4              0.25   Anonym, 1973
                         1963    1       0.04%          50 L        1.9    1.7     0.54   0.3            0.1      <0.1
                         1963    6       0.05%          50 L                              0.64   0.35             0.18

    Japanese    Japan            3       0.05%                                     0.3           0.11    0.05                    Anonym, 1980
    pear                         5       0 05%                                     0.44          0.16    0.09
                                 3       0.05%                                     0.48          0.16    0.03
                                 4       0.05%                                     0.58          0.1     0.08
                                                                                                                                             

    1 Colourimetric method was used for the determination.

    TABLE 8.  Residues of phenthoate in other crope resulting from supervised trials

                                                                                                                                               
                                              Application                         Residues in mg/kg, at intervals (days)             Reference
                                                                                             after application
    Crop       Country     Year      No.    rate %      formulation     0       1      6-7    13-14   20-21   21-26    34     70
                                          volume (1)
                                                                                                                                               

    Cabbage    Italy       1965      2      0.05            50 L                              <0. 1           <0.1                   Anonym., 
                                     6                                         3.18    0.11    0.09                                  1965

    Olives     Italy       1963      1      0.05/3000       50 L       10.9    8.1                     0.49   0.49            0.2    Anonym., 
                                                                                                                                     1963

    Onion      Japan                 2      0.05/1500                                          0.01                                  Anonym., 
                                     4                                                         0.01                                  1980

    Radish                           2      0.05/2000                                  0.005
                                     4      0.05/1500-2000             0.005           0.005                  0.005   0.005
                                     3      0.05/1800

    Spinach    Japan                 2      0 05/1500                                          0.015
                                     3      0:05/1500                                          0.018
                                     2      0 05/1500                                  0.005   0.015
                                     3      0:05/1500                                  0.007   0.005

    Tea/leaf   Japan                 2      0.05/2000                                                  0.008
                                     3      0.05/2000                                                  0.04
                                     2      0.05/3000                                                  0.04
                                     3      0.05/3000                                                  0.04

    Lettuce    Japan                 2      0.05/2000                                  0.08    0.08    0.02
                                     4      O.05/2000                                  0.06    0.05    0.09
                                                                                                                                               

    

    TABLE 9.  Carbon 14 residues in bovine tissue after feeding at a
    20 mg/kg level in the diet

                                                                
                     mg/kg in tissues after feeding for
    Tissue      8 days       18 days     26 days     26 days
                                                     7 days
                                                     withdrawal
                                                                

    Muscle      0.013        <0.033      <0.033      <0.033
    Fat         0.016         0.056       0.045      <0.045
    Kidney      0.324         0.408       0.502       0.116
    Liver       0.238         0.228       0.297       0.140
    Heart       0.028         0.061       0.087       0.052
    Brain       0.036        <0.042       0.054      <0.042
                                                                



    TABLE 10.   The penetration of 14C and 32P phenthoate into orange
    fruit, and the distribution of radioactivity in the surface wash,
    acetone extract and solid residue.

                                                                        
                                Percentage of the applied radioactivity
                                   recovered at indicated time (days)

                                   0        3       7      10     14
                                                                        

    14C-labelled phenthoate
    External surface wash         72.5    66.1     9.8     8.1    4.6
    Internal acetone extract1      -       5.4    15.6    12.8    7.8
    Solid residue1                27.5    21.7    21.6    34.7   28.3
    Total recovered              100.0    93.2    47.0    55.6   40.7

    32P-labelled phenthoate
    External surface wash         96.4    63.4    17.4    13.6   11.6
    Internal acetone extract1      -       5.9    22.0    24.2   18.2
    Solid residue1                 3.6    19.4    13.9    16.3   13.2
    Total recovered              100.0    88.7    53.3    54.1   43.0
                                                                        

    1 Includes peel only.  Radioactivity in pulp was less than 1% of
    the applied.

    TABLE 11.  Amount of 14C metabolites found in the surface wash and
    acetone extract of orange leaves after indicated time intervals

                                                               
    Compound found in      Percent of recovered radioactivity
    indicated material        after indicated time (days)
                              3       7       10      14
                                                               

    Phenthoate
    Surface wash              84.4    45.5    35.4    41.6
    Acetone extract            4.6    46.1    37.7    17.0

    Phenthoate
    Surface wash              0       0       2.8      5.1
    Acetone extract           0.2     0       7.2     12.4
                                                               



        TABLE 12.  32P Phenthoate equivalents (mg/kg) in treated apples, pears and olives

                                                                                                                       
    Time interval   External substances      Internal substances       Internal          Internal         Total
                    soluble in methanol      soluble in chloroform     substances        substances       internal +
                                                                       soluble           insoluble        external
                   Phenthoate  Other P32     Phenthoate  Other P32     in water          in chloroform    phenthoate
                               containing                containing                      and water        residue
                               substances                substances
                                                                                                                       

    Apples: var. Stark Delicious (0.02% solution)

     2 hrs.           1.00        0.21          0.17        0.04           -                  -           1.17
     1 day            0.26       traces         0.31        0.06           -                  -           0.57
    15 days           0.02         -            0.08        0.02         0.95               0.80          0.10
    29 days           0.00         -            0.00          -          0.96               0.69          0.00

    Pears: var. Trionfo di Vienna (0.04% solution)

     2 hrs.           1.35       traces         0.19        0.02           -                  -           1.44
     1 day            1.19       traces         0.40        0.05           -                  -           1.59
     4 days           0.33         -            0.26        0.09           -                  -           0.59
     9 days           0.19         -            0.12        0.07         0.43               0.18          0.31
    31 days1          0.006        -            0.01        0.02         0.16               0.09          0.016

    Pears: var. Passacrassana (0.045% solution)

     2 hrs.           1.23       traces         0.03        traces         -                  -           1.26
     1 day            1.01       traces         0.07        traces         -                  -           1.08
     5 days           0.55         -            0.05          -          0.04               0.02          0.60
    25 days1          0.28         -            0.16          -          0.39               0.07          0.44
    40 days2          0.20       traces         0.10        traces       0.34               0.14          0.30

    TABLE 12.  Continued...

                                                                                                                       
    Time interval   External substances      Internal substances       Internal          Internal         Total
                    soluble in methanol      soluble in chloroform     substances        substances       internal +
                                                                       soluble           insoluble        external
                   Phenthoate  Other P32     Phenthoate  Other P32     in water          in chloroform    phenthoate
                               containing                containing                      and water        residue
                               substances                substances
                                                                                                                       


    Olives /oils-yielding/: var. Leccino (0.05% solution)

     2 hrs.           11.16      traces         0.15        0.01         traces               -           11.31
     1 day             5.92      traces         1.50        0.36          0.10                -            7.42
     9 days            0.36       0.18          0.53        0.38          3.60              0.84           0.89
    30 days            0.19       0.03          0.06        0.35          2.58              0.86           0.25
    70 days            0.05        -            0.10        0.05          3.23              0.59           0.15
                                                                                                                       

    1 Fruit picking
    2 Pears of this winter variety were analysed after picking from trees
    and stored for 15 days at 19-20C.

    TABLE 13.  Phenthoate residue (mg/kg) detected in processed citrus by-products

                                                                                                                       
                                  ORANGE                        LEMON                            GRAPEFRUIT
                                                                                                                       

                      Phenthoate      Phenthoateoxon   Phenthoate     Phenthoateoxon    Phenthoate      Phenthoateoxon
    Unwashed peel     0.24-1.00       0.06-0.09        0.08-0.28      0.06-0.12         0.031-0.74        <0.01
    Washed peel       0.23-0.73       0.036-0.069      0.15-0.32        <0.01           0.23-0.51       <0.01-0.09
    Unwashed pulp     <0.002-0.031       0.01          0.003-0.024      <0.01           0.007-0.031       <0.01
    Washed pulp       0.005-0.011        0.01          0.002-0.004      <0.01           0.02-0.09         <0.01
    Chopped peel      0.34-0.67       0.01-0.03        0.08-0.26         0.03           0.26-0.49       0.002-0.051
    Peel frits        0.32-0.52       0.05-0.15        0.25-0.74      0.05-0.15         1.14-2.45       0.015-0.031
    Finisher pulp     0.008-0.015       <0.01          0.008-0.023      <0.01           0.003-0.008       <0.01
    Dried rind        0.13-0.43       0.01-0.036         2.2-2.7         0.01           0.72-1.51       0.06-0.21
    Press liquor      0.08-0.14       <0.01-0.01       0.008-0.032    0.009-0.017       0.13-0.19       0.01-0.013
    Emulsion water    0.004-0.07      <0.004-0.1       0.003-0.009     0.04-0.06        0.006-0.021       <0.01
    Fruit juice       0.002-0.003       <0.01          0.004-0.009       <0.01            <0.002          <0.01
    After-water rinse <0.002-0.004      <0.01          <0.002-0.005      <0.01            <0.002          <0.01
    Pre-water rinse   <0.002            <0.01             0.002          <0.01            <0.002          <0.01
    Molasses          0.047-0.068       <0.01           0.01-0.03        <0.01          0.037-0.071        0.01
    Oil               3.29-14.05      1.18-2.48         7.25-17.25    1.65-2.5            5.4-8.5       0.45-1.1
                                                                                                                       
    

    EVALUATION

    COMMENTS AND APPRAISAL

    Phenthoate is a wide-spectrum organophosphorus insecticide, mainly
    used on citrus at rates of 0.6 to 5 kg ai/ha.

    The technical material contains a minimum of 92% of phenthoate.
    Detailed analyses of the typical technical material, including the
    identity of the minor components, was provided.  It is generally
    soluble in most polar and non-polar organic solvents and also slightly
    soluble in water.

    Phenthoate is a cholinergic compound of moderately acute toxicity and
    is rapidly absorbed, metabolized and excreted in mammals.  The pattern
    of metabolism is similar in both plants and animals and is similar to
    that noted with other organophosphorus esters.  The rate of metabolism
    is shown to be significantly affected (with potentiation of toxicity)
    by organophosphorus esters commonly found as impurities in the
    technical product.  The acute toxicity of phenthoate is dependant on
    the purity of the technical product, a feature which raised
    significant questions about occupational exposure.  It was suggested
    that a more purified product should be manufactured and used to
    alleviate this problem.  Formulations that are stored also have the
    potential to become more toxic under certain conditions.  Although
    these factors do not directly affect phenthoate residues in food they
    should not be ignored.

    Phenthoate is moderately toxic to mammals.  The acute LD50 was noted
    to vary from 78 to over 4500 mg/kg bw, depending possibly on the
    impurities and the species.  Antidotal studies are not available.

    Phenthoate does not induce a delayed neurotoxic reaction in hens, is
    not mutagenic or teratogenic, nor does it interfere with reproduction,
    as evidenced by a standardized 3-generation study in rats.  In a
    series of short-term toxicity studies, cholinesterase depression was
    the most significant measure of effect of exposure.  In dermal and
    ophthalmological studies, phenthoate applied as a formulated product
    was irritating.  On the basis of available short-term studies, it is
    concluded that phenthoate is a potent cholinesterase inhibitor.

    A two-year study in the dog showing red blood cell cholinesterase
    depression served as the primary basis to evaluate a no-effect level.
    Phenthoate is not a carcinogen in mice.  A two.year study in rats was
    considered invalid and not included in the evaluation.

    On the basis of available data, no-effect levels in mammalian species
    were determined and a temporary ADI for man was allocated.  This
    evaluation was made on the assumption that the manufacture of
    phenthoate would be by a process that would assure that a product of
    at least 92% purity would be marketed.  As this was the product on
    which toxicological evaluations were made and as impurities have a

    substantial toxicological significance this purity restriction was
    important.

    Phenthoate residues gradually disappear from treated plants within 4
    to 10 weeks, most being lost by volatilization.  Decomposition of
    surface deposits is mainly due to photodegradation, resulting in
    phenthoate oxon as the main metabolite.  On cabbage, the surface
    residue 8 days after application consisted of 86% phenthoate but no
    oxon was detected; on orange leaves, 41.6% of the total residue was
    phenthoate and 5.1% was the oxon at 14 days after treatment.

    Phenthoate is not systemic but does enter the peel of fruit, where it
    undergoes hydrolytic cleavage and oxidation.  Virtually all of the
    residue remains in the peel of treated citrus fruit, the pulp
    containing less than 1% of the total residue.  Phenthoate oxon has
    been detected only in the peel.

    The main metabolites in plants, phenthoate oxon, dimethyl phenthoate,
    mandelic acid, bis-2-(carbethoxy) benzyl disulphide, O,O-dimethyl
    phosphorodithioic acid, O,O-dimethyl phosphorothioic acid and
    phenthoate acid, are similar to those secreted by animals.  Their
    amounts and relative proportions depend on the crop and the time
    elapsed since application but, in practice, the parent phenthoate
    should be considered as the only residue of importance.

    Repeated treatments of citrus fruits or apples according to
    recommended usage do not lead to increased residues or changed
    metabolite patterns.  The residue is contained mostly in the waxes and
    oils of the citrus rind and is not decreased significantly by washing;
    the fruit juice contains negligible residues.  Dried rind as used for
    cattle feed can contain 40 to 60% of the residue originally present in
    the peel.

    Laying hens fed for 30 days with feed containing 1.8 to 2.6 mg/kg of
    phenthoate showed no reduction of egg production or any abnormalities.
    Residues in the muscle and in eggs were low and disappeared after
    withdrawal of the compound from the diet; in kidney and liver levels
    reached a plateau between the third and seventh days of treatment.
    Neither phenthoate nor its metabolites accumulated in fish kept in
    water containing phenthoate at the 10-4 to 10-6 mg/l levels.

    Lactating cows given 14C-phenthoate at levels of 1.5 and 20 mg/kg in
    the feed excreted the material mainly in the urine and faeces.  The
    main metabolite was phenthoate acid, which accounted for 45% of the
    14C activity of the urine.  Residues in milk reached a plateau 2 to 3
    days after administration began.  The organosoluble fraction of the
    residue in milk, possibly phenthoate, phenthoate oxon and unconjugated
    metabolites, was very low (0.0028 mg/kg) even at the higher dosage
    rate.  Meat from the cattle contained traces of residues at the higher
    dosage rate only, the muscle tissue and the fat containing the
    residues in roughly equal proportions.  Residues in various tissues
    declined rapidly when the pesticide was withdrawn from the diet; even

    the bound (unextractable) metabolites were eliminated from kidney and
    liver.  Neither phenthoate nor its oxon could be detected in tissue or
    milk samples by conventional analytical methods at limits of
    determination of 0.05 and 0.01 mg/kg respectively. It was concluded
    that feeding cattle with citrus by-products prepared from
    phenthoate-treated fruit would not result in detectable residues in
    meat or milk.

    In soil, phenthoate is rapidly converted to phenthoate acid under both
    aerobic and anaerobic conditions, even when as much as 100 mg/kg is
    added to the soil.  Under conditions favourable for microbiological
    activity, such as adequate moisture and warm temperature, the soil
    type has no influence on the degradation of phenthoate.  On the other
    hand, phenthoate persists for a relatively long time under dry soil
    conditions.  Phenthoate and its metabolites show moderate mobility in
    soil, the majority of the residue being contained in the upper 15 cm. 
    The likelihood of contamination of lower soil layers or underground
    waters is very low in view of the high degradability and slow leaching
    properties of the residues.

    Analytical methods, based on GLC separation on columns of different
    polarity with flame photometric detection are available and suitable
    for regulatory purposes.

    Level-causing no toxicological effect in:

    Dog:    10 mg/kg in the diet equivalent to 0.29 mg/kg bw/day. 
    Mouse:  30 mg/kg in the diet equivalent to 4.5 mg/kg bw/day. 
    Rat:    10 mg/kg in the diet equivalent to 1.0 mg/kg bw/day.

    Estimate of temporary acceptable daily intake for man

    0-0.001 mg/kg bw/day.


    RECOMMENDATIONS OF RESIDUES LIMITS

    The meeting concluded that available information was adequate for the
    estimation of maximum residue levels for phenthoate on citrus fruits
    only.  The data on other crops were not considered adequate for
    estimating maximum residue levels.  The levels apply to the parent
    phenthoate excluding all metabolites.

                                                                        
    Commodity            Temporary maximum       Interval between last
                         residue level (mg/kg)   application and harvest
                                                 on which levels are
                                                 based
                                                                        

    Citrus fruit               1                           21
    Carcass meat of cattle     0.051
    Milk                       0.011
    Egg                        0.051
                                                                        

    1 At the limit of determination.


    FURTHER WORK OR INFORMATION

    Required (by June, 1984)

    A chronic toxicity study in an acceptable mammalian species (rodent).

    Desirable

    1.  Further information on impurities in the technical products in
    order to evaluate the degree to which these impurities potentiate the
    toxicity of phenthoate.
    2.  Data from supervised trials on other commodities in accordance
    with present uses of the compound.
    3.  Residue data from crops, known to have been treated under
    practical conditions, moving in commerce.


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    See Also:
       Toxicological Abbreviations
       Phenthoate (Pesticide residues in food: 1981 evaluations)
       Phenthoate (Pesticide residues in food: 1984 evaluations)